UCSD study: Autism begins in pregnancy

Autism begins before birth

Autism begins in pregnancy with subtle disruption of the brain's cortex, according to a study led by UC San Diego researchers. Moreover, it identifies a mechanism of abnormal gene activity explaining how the disruption causes autism.

If the study is confirmed, a physical cause will at last have been identified for autism, a developmental disorder whose origins are frustratingly vague. And a cause will give scientists a target for therapies and prevention. And further studies may find other brain abnormalities that have eluded discovery.

The study was published online Wednesday in the New England Journal of Medicine. Rich Stoner, Maggie L. Chow, and Maureen P. Boyle, all of UCSD, were first authors. Eric Courchesne of UCSD and Ed Lein of the Allen Institute for Brain Science in Seattle were senior authors.

The regions affected, the frontal and temporal cortex, are known to control social interaction and language skills, respectively. The normal organization of the cortex, the outermost part of the brain, was disrupted in patches in brain samples from 10 of 11 deceased children with autism, ages 2 to 15. Equivalent samples from 10 of 11 deceased nonautistic children didn't show this disruption. The cortex consists of six layers, which are established during pregnancy.

Brain cortex affected by autism

This UCSD video illustrates the regions of disruption in the cortex of those with autism.

Researchers found the patches by looking for 25 genetic markers found in brain cells, along with genes associated with increased risk of autism. Finding these signs in the brains of children is important because previous studies of adult brains may have missed childhood abnormalities, the study said. The brains of children with autism are enlarged, but the overgrowth disappears by adulthood.

"It's exciting, because it goes down to the molecular level," said Dr. Deepa Menon, assistant medical director at the Center for Autism and Related Disorders at the Kennedy Krieger Institute in Baltimore. This points to certain molecular things we might be able to start working on. Maybe we can start working on medications down the line."

It may turn out that autism is caused by an aberrant pattern of genetic activity that can be prevented, Menon said.

“It suggests that even though there’s heterogeneity in autism, some kids do better and some don’t, there may be some underlying biological pathology that gets the abnormal process going,” Courchesne said.

However, Courchesne said many more genetic markers need to be studied to completely map the autistic brain, probably hundreds.

“There’s more out there to be found, and there could be additional types of signatures of time of disruption and kind of disruption,” Courchesne said.

Dr. Thomas Insel, director of the National Institute of Mental Health, said the authors used advanced methods to examine cellular and molecular markers in more detail than previous research. But he said the study “highlights the critical need” for autopsy brain tissue to gain a better understanding of autism.

“If there really is this disorganized cortical architecture” in autism, it would develop before birth, said Insel. NIMH helped pay for the research.

Autism is a spectrum of neurological disorders that affect social interaction ability. One out of 88 children who are 8 years old have autism, according to the Centers for Disease Control and Prevention. About 20 to 30 percent of those with autism develop epilepsy by adulthood.

In its most severe form, those with autism never learn to speak, ignore others, and engage in repetitive and stereotyped behaviors. This behavior becomes apparent in early childhood.

At the other end of the spectrum, called high-functioning autism or Asperger syndrome, those affected find social interaction difficult and often frustrating. They usually have average or above-average intelligence, and may excel in fields that emphasize solitary work.

Autism, what it is, what causes it and how to treat it, has been an intensely controversial subject for decades. Researchers have looked for causes in genetics and in the environment, but the picture is incomplete. Some gene variants have been identified as risk factors for autism, but the correlation is far from universal.

"Researchers have been trying to figure out how the genetic information that we've gotten affects brain growth in children with autism," Menon said. "If you just take a regular MRI, you don't see any changes. This study tries to pinpoint where the genes might be affecting brain growth at a micro-level. It links the genetic findings and the imaging findings together."

Last year, researchers reported that 23 percent of autism cases are linked to a specific combination of antibodies in the mother's blood. These antibodies target the fetal brain. Women with the antibodies are 99 percent likely to give birth to a child with autism.

Pediatric Bioscience is developing a blood test to inform women whether they have that antibody combination before they conceive. It could also help in early diagnosis of infants with autism.

Other funders of the study include the Simons Foundation, the Peter Emch Family Foundation, Autism Speaks, The Thursday Club Juniors, and the Allen Institute for Brain Science.